September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Full field ERG responses and fundus autofluorescence of Stargardt patients harboring different non-null ABCA4 alleles in trans with null alleles
Author Affiliations & Notes
  • Ana Fakin
    UCL Institute of Ophthalmology, London, United Kingdom
    Moorfields Eye Hospital , London, United Kingdom
  • Anthony G Robson
    UCL Institute of Ophthalmology, London, United Kingdom
    Moorfields Eye Hospital , London, United Kingdom
  • Michel Michaelides
    UCL Institute of Ophthalmology, London, United Kingdom
    Moorfields Eye Hospital , London, United Kingdom
  • John (pei wen) Chiang
    Casey Molecular Diagnostic laboratory, Portland, Oregon, United States
  • Anthony T Moore
    UCL Institute of Ophthalmology, London, United Kingdom
    Moorfields Eye Hospital , London, United Kingdom
  • Graham E Holder
    UCL Institute of Ophthalmology, London, United Kingdom
    Moorfields Eye Hospital , London, United Kingdom
  • Andrew Webster
    UCL Institute of Ophthalmology, London, United Kingdom
    Moorfields Eye Hospital , London, United Kingdom
  • Footnotes
    Commercial Relationships   Ana Fakin, None; Anthony Robson, None; Michel Michaelides, None; John (pei wen) Chiang, None; Anthony Moore, None; Graham Holder, None; Andrew Webster, None
  • Footnotes
    Support  NIHR grant, NIH/NEI EY021163 and NIH/NEI EY019861
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 6589. doi:
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      Ana Fakin, Anthony G Robson, Michel Michaelides, John (pei wen) Chiang, Anthony T Moore, Graham E Holder, Andrew Webster; Full field ERG responses and fundus autofluorescence of Stargardt patients harboring different non-null ABCA4 alleles in trans with null alleles. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6589.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To explore the phenotype of Stargardt patients harboring non-null ABCA4 alleles in trans with null alleles and thence determine the effect of specific alleles.

Methods : 68 patients, drawn from a database of 480 genetically confirmed Stargardt patients, carried a non-null ABCA4 allele in trans with a likely-null allele (truncating mutation, c.5461-10T>C or c.6729+4del15). 19 patients with two likely-null alleles in trans were examined in parallel as a comparison nullizygous group. Full-field ERG was performed and the patients classified into ERG groups 1-3 (Lois et al, 2001). The dark adapted standard strong flash stimulus a-wave amplitudes were plotted against age and compared with 95% confidence interval (nCI) of the nullizygous group. Fundus autofluorescence imaging (FAF; Spectralis, Heidelberg, Germany) was assessed when available.

Results : Alleles p.G1961E (N=16, 5-51y) and p.R2030Q (N=2, 64 and 49y) were associated with a normal full field ERG (group 1). Most p.G1961E patients had foveal atrophy with flecks localized at its border. Both p.R2030Q patients had irregular autofluorescence, extending beyond vascular arcades, with small regions of perifoveal atrophy. Five alleles (p.R24H, p.G863A or 863delG, p.P1380L, p.L2027F and c.5714+5G>A; N=36, 9-75y) were associated with normal (ERG group 1, N=18) or abnormal (ERG group 2 or 3, N=18) ERG with amplitudes outside the nCI in 31/36 cases. The 18 cases with normal ERGs were younger than those with retinal dysfunction (avg. 28 vs. 43 years, p<0.005). Six alleles (p.L541P/A1038V, p.E1022K, p.C1490Y, p.E1087K, p.T1526M, and p.C2150Y; N =14, 9-67y) were consistently associated with abnormal ERGs (group 2 or 3) with amplitudes comparable to nullizygous patients (14/14 within the nCI). Most patients from the second and third group had irregular FAF extending beyond the arcades, with patients from the second group having larger areas of atrophy compared to similarly aged patients from the third group.

Conclusions : When in trans with a null allele, 2/13 ABCA4 variants were associated with preserved peripheral retinal function, 5/13 alleles were associated with either preserved or mildly abnormal retinal function that tended to be worse in older patients, and 6/13 behaved similarly to nulls. It is hypothesized that this represents distinct degrees of retained ABCA4 protein function of the studied alleles.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

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